JPS63233010A - Novel aluminum hydroxide gel and its utilization - Google Patents

Abstract

PURPOSE:To obtain an Al(OH)3.gel consisting of a specified compd. and useful in a field of application wherein said gel is used as an excellent antacid for acid in stomach, an acid adsorbing agent and a cation exchanger. CONSTITUTION:A soluble Al compd. (e.g. AlCl3) consisting of water-soluble and/or lower alcohol soluble salt, and a soluble compd. of a source for supplying carbonic ion (e.g. Na2CO3) are brought into reaction at pH6-9.5 at 20-50 deg.C so that molar ratio of CO2/Al in the Al(OH)3.gel obtained by the reaction become >=0.1. Then, the Al(OH)3.gel contg. <=2wt.% alkali metal and expressed in inequality I [wherein, M is alkali metal such as Na, K; x1-3 is the relation expressed in inequalities II-VII, respectively; (y) is positive number in the formula VIII, (m) is positive number in inequality IX] is formed by ion- exchanging the alkali metal contained in the obtained compd. with Ca, or Ca and Mg. The tablet of antacid, etc., is prepared by mixing said Al(OH)3.gel with a desired ecipient, etc., if necessary, and then is utilized for adjusting acidity for acid in stomach by dosing at the rate of 2-5g/day.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an aluminum hydroxide gel containing calcium hydroxide as an essential component, which has not been published in any prior literature, and its use.
For example, when used as an antacid, it exhibits improved properties compared to conventionally known aluminum hydroxide gels, such as a higher reaction rate to stomach acid, superior aging resistance, and no fear of side effects. It is useful in the fields of use as acid agents, acid adsorbents, cation exchange agents, etc., and many improvements are expected in its use as antacids.

More specifically, the present invention relates to the following formula (I), [(CaO)
-I(lJgo) -2(M2O) -3]A 12O
3 (CO2)y-mHz.

However, in the formula, M represents an alkali metal such as Na, xl is O<x,<1 X, is O≦x2kuI X, is 0≦x3〈1 and X co<XI X 3 (X.

0x++x, +xx-x<1 y is 0.2<y≦1 m is a positive number of 2≦m<10
) compound as an active ingredient.

Aluminum hydroxide gel is a typical antacid that is still widely used today. The main reason for this is that it has very few side effects on the human body. However, conventional aluminum hydroxide gels have a slow reaction rate to acids and age relatively rapidly after being manufactured, so that when a user takes them, they do not have the pH of the stomach acid required as an antacid. It ages to the extent that it takes about 10 minutes or more to neutralize to about 3 or more, and furthermore, the amount of acid neutralization is low and it cannot function as an antacid.

Antacids have the ability to quickly neutralize the pH of stomach acid, which is around 1.2, to a pH of approximately 3 to 5, and are resistant to maintain this function for a long period of time after manufacture. It is desired that the material exhibits aging properties. However, conventional aluminum hydroxide gels are unsatisfactory both in terms of reaction rate to acids and aging properties.

The present inventor has conducted research to provide an aluminum hydroxide gel that overcomes these difficulties. the result,
It has been discovered that an aluminum hydroxide gel having calcium as an essential component and represented by the above formula (I), which has not been previously described in any literature, can exist and can be easily produced. Furthermore, this new aluminum hydroxide gel exhibits significantly improved acid reaction rate and aging resistance, and also has improved properties that make it suitable for use as an antacid without the risk of side effects. Furthermore, it has been discovered that the aluminum hydroxide gel is useful in a wide range of applications such as acid adsorbents, cation exchangers, and others.

Conventionally known aluminum hydroxide gel is expressed by the following formula % formula % where p is O<p≦2 q is 0.2≦q≦2 r is a positive number of 2≦r≦3 Modified aluminum hydroxide gels are known and have improved acid reaction rate and aging resistance compared to regular aluminum hydroxide gels (see Comparative Examples 1 and 2 below). However, the above-mentioned formula (I) aluminum hydroxide gel of the present invention is different from the above-mentioned known modified aluminum hydroxide gel.
It was discovered that it exhibits even more surprising acid reaction rate and aging resistance improvement properties than gels (see Example 1 and Comparative Example 1 below).

Moreover, in the formula (I) aluminum hydroxide gel of the present invention, the alkali metal content in formula (I) can be reduced to about 2% or less, even as low as 0%, based on the weight of the formula (I) compound. It has been found that it is possible to advantageously avoid the risk of renal damage and hypertension-inducing side effects derived from the K and Na of the above-mentioned known modified aluminum hydroxide gel.

It is therefore an object of the present invention to develop a novel aluminum hydroxide
There is a gel to provide.

Another object of the present invention is to provide the use of the aluminum hydroxide gel.

The above objects and many other objects and advantages of the present invention will become more apparent from the following description.

The novel aluminum hydroxide gel of the present invention has the following formula (I
).

[(CaO) w + (MgO) t! (I42
O) w s ] Al zos (Cow ))' ”
mHx.

However, in the formula, M represents an alkali metal such as Na, x, is O < x, < 1 X2 is 0≦x3<1 X, is 0≦xs<1 and xs(x.

X3<X2 0<Xl+X! +X3-X<1, preferably 0.2≦x
<0, 8, more preferably 0, 4<x<0, 6°y is 0.2<y≦1, preferably 0.4≦y≦0.8, more preferably 0.6≦y≦0 .8°m indicates a positive number of 2≦m<10.

Although Ca is an essential component in the aluminum hydroxide gel of the present invention, it may also contain Mg and alkali metals such as N@ and K.

The content of Mg can be freely changed, but preferably Ca is equal to or more than the mole of Mg, that is, in the formula (I), x, /xz is 1 or more, more preferably xl/x,
is 4 or more.

Furthermore, in the above formula (I), the alkali metal is represented by the formula (I
), preferably about 2% or less, more preferably about 1.5% or less, based on the weight of the compound.

When using aluminum hydroxide gel as an antacid, it is required that the alkali metals that cause renal damage and hypertension, usually K and Na, should be less than about 3%, and the liquid content should be less than 1O. (e.g., United States Pharmacopeia,
British Pharmacopoeia) is required. In the aluminum hydroxide gel of the formula (I) of the present invention, the troubles of the alkali metal content and high liquid properties in known modified aluminum hydroxide gels can be completely avoided. Furthermore, Ca.

Mg itself is an effective antacid active ingredient, and is also a component with extremely few physiological side effects, and no side effects occur within the composition range shown in formula CI).

Further, the aluminum hydroxide gel of formula (I) of the present invention contains Ca
and Mg can be converted to formula (I) by ion exchange with an alkali metal.
Aluminum hydroxide does not combine into compounds to form calcium carbonate or basic magnesium carbonate.
A clear distinction can be made between gels and mixtures of these compounds. Furthermore, the aluminum hydroxide gel of formula (I) of the present invention is
N a A 1 (OH)z, a known crystalline compound
It can be clearly distinguished from cOs (dawsonite) because it is a substantially amorphous compound in its X-ray diffraction image.

Although it is not necessarily clear why the aluminum hydroxide gel of formula (I) of the present invention exhibits significantly improved acid reactivity and aging resistance compared to conventionally known aluminum hydroxide gels, the present invention They speculate as follows. Of course, it should be understood that the present invention is not limited by such speculation.

In other words, in conventional aluminum hydroxide gel, most of the carbonate ions bonded to aluminum are monovalent, so the bonding strength is weak, and therefore it is easily hydrolyzed and converted to aluminum hydroxide. It is thought that it will happen. Therefore, the hydrolysis of conventional aluminum hydroxide gels progresses more easily during storage, especially under high temperature and humid conditions, so the antacid activity gradually decreases after production. I will continue to do so.

However, in the aluminum hydroxide gel of formula (I) of the present invention, carbonate ions are converted to divalent ions, and as a result, the bond with aluminum is strengthened, and it is presumed that hydrolysis hardly occurs. Ru. This effect is considered to be that when K and/or Na is ion-exchanged with Ca or Mg, the latter has a stronger binding force and is therefore more resistant to hydrolysis. Since these Ca and/or Mg react with acid faster than AI, the acid reaction rate is lower than that of conventional aluminum hydroxide gel.
It is assumed that it will be faster.

The formula (I) aluminum hydroxide gel of the present invention can be prepared, for example, by combining a soluble aluminum compound and a carbonate ion source soluble compound such that the CO*/A 1 molar ratio of the formed aluminum hydroxide gel is about 0. It can be produced by reacting the compound at a pH of about 6 to about 9.5 and ion-exchanging the alkali metal of the resulting compound with calcium or calcium and magnesium.

There are no particular restrictions on the reaction temperature, but a temperature of about 2O to about 50C can preferably be used. Generally, the amount of carbonate ion supplied relative to aluminum is preferably as large as possible; however, if it is too large, the aluminum content will be 40% or less, which is undesirable because the amount of acid neutralization will be low. On the other hand, if it is too small, the acid reaction rate and aging resistance will decrease, which is not preferable. Therefore, the supply molar ratio of carbonate ions to aluminum, COt/A I, is approximately 0
．． It is preferable to carry out the reaction by adjusting the ratio to 1 or more and about 8 or less, preferably about 0.5 or more and about 3 or less.

The pH of the reaction system is at least the pH at which divalent carbonate ions exist, and at which aluminum hydroxide is difficult to form.
It is preferable to appropriately select a pH range in which the ion exchange reaction with alkali metals mainly occurs due to Ca, and the formation of their hydroxides hardly occurs, for example, from about 6 to about 9. An example is a range of 5. More preferably the pH is about 7 to about 9.

As the soluble aluminum compound (in the present invention, the name includes aluminum metal) used in the above reaction, water and/or lower alcohol soluble salts can be preferably used, such as aluminum chloride, aluminum nitrate, aluminum sulfate, aluminum Examples include metals, ammonium aluminum sulfate, aluminum bromide, aluminum fluoride, potassium aluminum sulfate, aluminum isogloboxide, sodium aluminate, potassium aluminate, sodium aluminum sulfate, and the like. Further, as the carbonate ion source soluble compound used in the above reaction, carbonate ion supplying compounds soluble in water and/or lower alcohol can be preferably used, such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc. In addition to alkali metal carbonates and bicarbonates, carbon dioxide gas, urea, etc. can be exemplified.

Furthermore, examples of the alkaline substances used for the pH adjustment include ammonia, ammonium hydroxide, sodium hydroxide, potassium hydroxide, and the like.

The reaction between the soluble aluminum compound and the carbonate ion source soluble compound can be carried out in water and/or a lower alcohol solvent. The ion exchange reaction in which the alkali metal of the obtained compound is ion-exchanged with calcium or calcium and magnesium can be carried out using a known ion exchange reaction means. For example, a method can be used in which the obtained compound is brought into contact with an aqueous solution containing Ca and Mg ions, or a method in which a cake of the compound is formed and then washed with an aqueous solution containing Ca and Mg ions.

Although there is no particular restriction on the concentration of the aqueous solution containing Ca and Mg ions, it is preferably used at a concentration of about 0.1 to 1 mol/Q. Examples of soluble Ca- and Mg-containing compounds used to form such a Ca- and Mg-ion-containing aqueous solution include calcium chloride, calcium nitrate, calcium fluoride, magnesium chloride, magnesium nitrate, magnesium sulfate, magnesium fluoride, and iodide. Examples include magnesium, concentrated seawater, and bittern. For example, the aluminum hydroxide gel of formula (I) of the present invention obtained as described above is useful in a wide range of fields in which aluminum hydroxide gel is used as an acid adsorbent, a cation exchange agent, and in particular, It exhibits excellent performance when used as an antacid.

Thus, according to the present invention, an antacid characterized by containing the compound of formula (I) as an active ingredient can be provided.

In this use, the drug layer can be freely selected, and can be, for example, a powder, granule, granule, tablet, suspension, syrup, or the like.

Additionally, any commonly used diluents, excipients, lubricants,
A disintegrant or the like can be used. Furthermore, it can also be in the form of a mixture with other drugs. The dosage can be selected as appropriate, for example, about 2 g to about 5 g/day.

Hereinafter, the invention aluminum hydroxide gel,
Several examples of its manufacturing method and effects will be more specifically illustrated.

Example 1 A 500+xffi fishing rod is placed in a cylindrical stainless steel reaction tank with a capacity of Iff and equipped with an overflow device, and stirred sufficiently with a Chemister stirrer.

A metering pump was added to this reaction tank at 300C±1.
Aluminum sulfate aqueous solution (AI,
O, 0.9 mol/ff), sodium carbonate aqueous solution (0.6 mo!/(2)), and sodium hydroxide aqueous solution (2.0 mol/ff) at a total flow rate of approx. The reaction was carried out for about 1 hour by feeding at a rate of 200 mα/min.

The suspension obtained by overflowing Cot/AI zOs-2, pH-7,5±0.2 was dehydrated under reduced pressure with Nutsche to form a cake, and then 0.05 mol
/I2 using an aqueous calcium chloride solution, A110. Ion exchange was performed by washing with an amount equivalent to 50 times the weight of the content. Thereafter, it was washed with water and dried at about 70° C. for 20 hours.

As a result of chemical analysis, the obtained aluminum hydroxide gel had the following composition.

(MgO). +5A1zOs・(Gori.6°4.7H
! The sodium content of the gel was 0.10%.

Also, X-ray diffraction results showed that it was substantially amorphous. Furthermore, the refractive index by Larsen's oil immersion method is 1
．． It was between 422 and 1.443. The refractive index of the sodium-containing compound present in trace amounts is 1.430 and 1.495.
It was between. Note that the refractive index of conventional aluminum hydroxide gel is between 1.495 and 1.72O.

The resulting aluminum hydroxide gel was treated with 0% of U.S. EDA.
, T, C (over-the-counter
) Its acid reactivity and aging resistance were evaluated according to the antacid test.

The results are shown in Table 1 below.

(I) Acid reactivity test method In a 100 mQ beaker, 0. 1N-HCl 50mQ
Accurately take a sample, immerse it in a 37°C constant temperature bath, and bring the liquid temperature to 37°.
After adjusting to C, stir with a magnetic stirrer (2
40 r, p, m) Immerse the electrode of the pH meter in the liquid. Add 0.8 g of sample powder, and at the same time start the time with a stopwatch to measure the time until the pH reaches 3 and 3.5 and the pH 10 minutes later.

(2) Aging condition The knee sample was placed in a desiccator containing saturated saline and left at 60°C for 7 days. Aging resistance is measured by conducting the acid reactivity test described in (I) above on a sample after undergoing the above aging conditions.

Comparative Example 1 In Example 1, the sample was washed with water and then dried at 70° C. for 20 hours before ion exchange with calcium chloride.

This sample contained 5.5% sodium. -The liquid acid reactivity and aging properties of this sample are shown in Table 1 below. If the liquid property exceeds IO, it cannot be used as an antacid. The refractive index of this material was 1.480-1.495.

Comparative Example 2 The liquid properties, acid reactivity, and aging test results of commercially available aluminum hydroxide gel are shown in Table 1 below. Note that the sodium content of this product was 0.1%.

Example 2 Aluminum chloride aqueous solution (1-O as Ar2Os)
mol/Q), potassium carbonate aqueous solution (0.5mat/(
2), the reaction was carried out in the same manner as in Example 1 under the following conditions. Reaction temperature 20°C, molar ratio of carbonate ions to aluminum Go! / Alx0s-5, 1, pH-7
, 5 ± 0.2° The obtained precipitate was dehydrated under reduced pressure to form a cake, and then ion exchange membrane method bittern (mixed aqueous solution of magnesium chloride and calcium chloride: Mg''-0,14mo I/Q, Ca7
”-0,06mo I/Q), A 1 to
Ion exchange was performed using a liquid volume equivalent to 40 times the s content. Thereafter, it was washed with water and dried at 70° C. for about 20 hours.

The chemical composition of this product was as follows.

(CaO)o, I s(Mgo)s, os”Alz
os'(Co,)o,ya''2.5H,0The sodium content was 0.05%. Powder X-ray diffraction was measured and it was found to be amorphous.The acid reactivity test results of this material were It is shown in Table 1 below.

Furthermore, the results of the acid reactivity test and aging resistance test conducted using artificial gastric juice 1 having the following composition are shown in Table 2 below.

Claims (1)

[Claims] 1. The following formula (I), [(CaO)_x_1(MgO)_x_2(M_2O)
_x_3] Al_2O_3(CO_2)y・mH_2O
However, in the formula, M represents an alkali metal such as Na or K; = x < 1 y is 0.2 < y < 1 m is a positive number of 2 < m < 10 Aluminum hydroxide gel represented by these. 2. In the formula (I), the amount of the alkali metal is determined by the formula (I
2.) The aluminum hydroxide gel of claim 1, wherein the aluminum hydroxide gel is about 2% or less, based on the weight of the compound. 3. In the formula (I), x is 0.2≦x<0.8 y is 0.4≦y≦0.8 m is 2≦m<10 Claim No. Aluminum hydroxide gel according to item 1. 4. The following formula (I), [(CaO)_x_1(MgO)_x_2(M_2O)
_x_3] Al_2O_3(CO_2)y・mH_2O
However, in the formula, M represents an alkali metal such as Na or K; = x < 1 y is 0.2 < y < 1 m is a positive number of 2 < m < 10 An antacid characterized by containing a compound represented by these as an active ingredient. 5. In formula (I), the amount of the alkali metal is determined by formula (I
5.) The antacid of claim 4, wherein the antacid is about 2% or less, based on the weight of the compound.